Circulating tumor cells predict early skeletal-related events in patients with bone metastases from breast cancer

Background: Bone metastases and following skeletal-related events (SREs) are frequent in metastatic breast cancer (MBC) and are a major cause of disability. Circulating tumor cells (CTCs) are prognostic in MBC and are more frequent in patients with bone metastases (BMs). We investigated whether CTCs could be quantitative predictive factors of SREs in this setting. Methods: CTC analysis was performed using CellSearch technology within the first month of BM diagnosis and blood samples containing ≥5 CTCs/7.5 mL were considered positive. Patients were then prospectively followed-up until first onset of a SRE or death. Results: In 145 BM-MBC patients, mean CTC number was 295/7.5 mL and 60% of patients had ≥5 CTCs. SREs occurred in 82 (57%) patients. After a median follow-up of 105 months, median time-to-SRE (TT-SRE), progression-free survival (PFS) and overall survival (OS) from CTC analysis were 18, 5, and 14 months, respectively. In multivariable analysis, CTCs ≥5 predicted a shorter TT-SRE (median ttSRE 11 vs 31 months, HR 2.08, 95%CI 1.26-3.40, p .004). CTC ≥5 were also an independent predictor of shorter PFS (HR 2.72, 95%CI 1.86-3.95, p < 0.0005) and worse OS (HR 3.16, 95%CI 2.183-4.576, p < 0.0005). Conclusion: In this series of MBC patients with BMs and a long follow-up, the detection of CTCs in peripheral blood was not only associated with a worse prognosis in terms of PFS and OS, but was also predictive of an increased risk of skeletal-related events.